The incidence of esophageal adenocarcinoma is rising faster than for any cancer in the U.S, and is the sixth leading cause of death from cancer in men. Esophageal adenocarcinoma is believed to arise from a condition known as Barrett's esophagus (BE) in which the esophageal epithelium is marked by abnormal intestinal-type cell growth, also believed to result from chronic gastroesophageal reflux disease (GERD). Although it is unknown whether BE is a necessary precursor to all cases of esophageal cancer, it is a well documented and clearly recognized risk factor for esophageal adenocarcinoma. As will be evident in the exemplary image shown in FIG. 1, BE mucosa tissue 10 appears salmon pink in color, in contrast to the normal pearly white squamous mucosa 12 of an esophagus 14 (these tissue types are shown by gray scale, which only indicates color). Although screening for esophageal cancer is not deemed appropriate for the general population, periodic examination of patients with BE is recommended in order to identify dysplasia or cancer at an earlier and more treatable stage. While standard endoscopy and tissue biopsy are sufficient for the monitoring of patients diagnosed with BE, 95% of esophageal adenocarcinoma develops in patients with previously undiagnosed BE, proving that current endoscopic screening efforts are inadequate.
When considering a screening strategy for a condition such as BE, it is important to consider several factors: disease progression, availability of screening resources, performance of a particular screening test (sensitivity and specificity), accessibility to treatment, the willingness of patients to undergo screening, and the associated cost. BE is a fairly common condition among patients having the symptom of heartburn, with an estimated prevalence ranging from 6%-12%. Currently, screening is performed using a standard gastrointestinal (GI) endoscope on a sedated patient to examine and biopsy any abnormal appearing mucosa. An assessment of the presence of BE by an endoscopist has been shown to have a relatively high sensitivity and specificity when compared to pathologic confirmation. The additional use of topically-applied dyes for chromoendoscopy, expanded magnification, and separate analysis from narrow-band excitation may improve the sensitivity and specificity for BE, though their clinical utility is currently unproven. Once diagnosed, BE is treated by reducing the symptoms of GERD using pharmaceuticals and/or surgery with new highly successful therapies being developed specifically for BE. While there are no randomized studies demonstrating that screening and surveillance improve BE patient outcomes, retrospective cohort studies suggest that BE patients undergoing surveillance have significantly improved survival compared to controls.
In a physician survey, 62% indicated that if unsedated endoscopy were made available to primary care physicians in an office setting, an increase in BE screening would result. Unsedated endoscopy using a thinner endoscope is an alternative to standard endoscopy, but is not commonly used in the USA, possibly due to patient lack of acceptance of the common transnasal approach. Finally, there is ongoing research aimed at finding biomarkers that identify esophageal adenocarcinoma in its pre-cancerous and neoplastic stages, since it is believed that genetic changes precede any morphological changes found during histological analysis. However, at present, there is no single biomarker available for which a negative indicator test result would warrant discontinued screening of a patient.
Ideally, a new screening test for BE should be as sensitive and specific as standard endoscopy, but should not require sedation and should have low risk and low cost. The current cost for standard endoscopy that has been indicated by the Center for Medicaid and Medicare Services (CMMS) is several hundred dollars, excluding biopsies. The CMMS cost for esophageal capsule endoscopy is even higher. Nevertheless, screening and monitoring with standard endoscopy followed by esophagectomy for surgical candidates with high-grade dysplasia or cancer, or endoscopic therapy for cancer patients who were not operative candidates has been reported to be cost-effective.
Wireless capsule endoscopy or “pill” endoscopy is a recent alternative to standard endoscopy, which uses a modified capsule containing two cameras, a battery source, and a wireless transmitter for sending images to an external digital recorder. However, untethered capsule endoscopy is limited because it yields random views of the esophagus, produces images at sub-video frame rates (˜2 per sec), and increases the overall cost of diagnosis. It would be preferable to employ a tethered capsule to achieve direct control over a camera view by an endoscopist, enable imaging at near video frame rates, and reduce overall cost. Furthermore, there is a need to provide images in a mosaic format, in which the inner surface of the esophagus (or other body lumens to which the technique is applied) can be viewed as an unrolled, flat image over an extended longitudinal depth.
Accordingly, it would be beneficial to employ a new low-cost device specifically for BE screening and for imaging inside the esophagus and other types of body lumens that is based on a completely new type of endoscope imaging technology. Instead of using passive illumination and a CCD array for image capture, it would be desirable to employ a single optical fiber to scan a surface using laser illumination, while responding to backscattered light, which is recorded one pixel at a time to form an image. The fiber scanner and lenses used for imaging should be housed within a capsule that is coupled to a tether comprising a single optical fiber employed for illumination, as well as scanner drive lines, and a plurality of return plastic optical fibers. In a manner similar to standard endoscopy, a base station can be provided that contains light sources as well as optical detectors and software needed to provide a machine vision software tool for clinicians. In order to judge short (<3 cm) versus long segment BE, it should be possible for clinicians to measure the extent of suspected BE above the top of the gastric folds.
In addition, if conventional imaging devices are used instead of the new type of imaging device noted above, software running on a system coupled to the imaging device should still enable a mosaic of the entire esophagus inner surface (or the inner surface of other types of body lumens) to be automatically generated from the images provided by the device to aid a clinician in visualizing the extent of BE and identify likely sites for future biopsies. A virtual colonoscopy using computed tomography and a new mosaic panorama perspective should enable a radiologist to read a patient's data significantly faster than relying upon a conventional virtual colonoscopy perspective, without detriment to detection rate. The laser-scanning imaging provided by an imaging probe and the application of integrated mosaicing software should thus be useful for screening and surveillance of neoplasia and other diseased tissues within a lumen more efficiently and at lower cost than can be achieved with conventional techniques.